Providing Fertility Care to HIV-1 Serodiscordant Couples: A Biologist's Point of View

Mark V. Sauer (2003) makes an important contribution to a growing argument for provision of assisted reproductive technology to human immunodeficiency virus type 1 (HIV-1)-infected individuals and provides insight into his pioneering work with HIV-1 discordant couples in the United States. Sauer's program offers intracytoplasmic sperm injection (ICSI) to couples in which the man is HIV-1 infected and the partner is uninfected. He argues that this approach offers the best protection against HIV-1 infection of the partner and baby because minimal numbers of potentially HIV-1-infected inseminating sperm are used.

Our research and that of others has shown that HIV-1 in semen is primarily found in the white blood cell and cell-free (seminal plasma) compartments of semen (Quayle et al. 1997) and that careful application of conventional sperm separation/wash techniques, such as density centrifugation and/or swim-up, can reduce levels of HIV-1 in the inseminating motile sperm fraction by more than 10,000-fold (Chrystie et al. 1998; Hanabusa et al. 2000; Lasheeb et al. 1997; Marina et al. 1998; Marina 2001; Tachet et al. 1999). Published data from 267 HIV-1- infected subjects indicate that HIV-1 RNA transcripts in unfractionated semen range from undetectable to over 10,000,000 copies, with study medians ranging from undetectable to 10,000 copies (Politch and Anderson 2002a). These data indicate that conventional sperm separation/wash techniques will reduce HIV-1 RNA levels to undetectable in a majority of cases. Studies in which HIV-1 RNA levels have been measured in the motile sperm fraction after processing have indicated that low levels of HIV-1 RNA are detectable in 3.6% (22 HIV-1 RNA positive out of 607 total) of samples (Marina et al. 2001). Since most HIV RNA transcripts are associated with noninfectious virus particles and documented titers of infectious HIV-1 particles in semen are considerably lower than RNA copy number (range: 0 to 100), low levels of residual HIV-1 RNA in the inseminating fraction are probably clinically insignificant. However, more research is needed to establish this as fact. We advocate a conservative approach: screening processed samples for HIV-1 and other sexually transmitted pathogens by sensitive molecular tests prior to their use for insemination, and minimizing the number of inseminations. In these two aspects the ICSI approach is superior to intrauterine insemination (IUI) and in vitro fertilization (IVF) procedures. Selecting a single sperm from a sample containing thousands of sperm that have tested negative for HIV-1 RNA (usual cutoff in molecular tests: 400 copies/sample) provides additional insurance that the inseminating sperm will be HIV-1 negative; furthermore, ICSI pregnancy rates per cycle in HIV-1 discordant couples are about twice that of IUI rates (medians of published studies: 39.5 versus 18.2) (Politch and Anderson 2002a; Politch and Anderson 2002b; Sauer).

However, there is at least one biological caveat with the ICSI approach. Several investigators have documented an apparent association between HIV-1 virions or DNA and sperm (Piomboni and Baccetti 2000). Quantitative molecular data indicate that this is a rare occurrence (Quayle et al. 1998), but HIV-1 that is on or inside spermatozoa may be particularly infectious or harmful. Baccetti et al. (1994) and Kiessling (1998) have provided evidence that human oocytes and mammalian embryos can be infected by HIV-1, and it has also been documented that sperm can introduce foreign DNA into the embryo, where it can integrate into host DNA and have deleterious effects (Gordon 2002). With the ICSI procedure, a single sperm is injected directly into the egg cytoplasm, bypassing at least two mechanisms that can protect against sperm-borne pathogens and DNA:

1. the acrosome reaction, during which sperm shed their outer membranes (and...